Diazepam
Diazepam. Prototype benzodiazepine — GABA-A PAM. Very long effective t½ via active metabolites (desmethyldiazepam, oxazepam) — accumulation in… Oral half-life 43 h.
Prototype benzodiazepine — GABA-A PAM. Very long effective t½ via active metabolites (desmethyldiazepam, oxazepam) — accumulation in elderly + chronic dosing. Muscle relaxant activity notable.
PK: the intravenous row was filed under an ORAL-ONLY study, and the stored 20 h was that study CYP2C19 wild-type SUBGROUP of six subjects — its other genotype arms give 62.9 and 84.0 h, so a population value it is not. The record also contradicted its own mechanism text, which names desmethyldiazepam at 99.2 h. Re-sourced: half-life 43.3 h and Vss 1.26 L/kg (88 L at 70 kg, a true intravenous volume) from PMID:6784999, six healthy young subjects on 10 mg intravenously; oral F 0.94 from PMID:6849499, 22 volunteers aged 20 to 78 dosed orally against intravenous. THE PARENT HALF-LIFE UNDERSTATES DURATION: desmethyldiazepam runs 99.2 h in the same wild-type subjects (PMID:10613621), which is kept as a metabolite citation only. ka 2 /h dropped; the 0.9 h beside it is a Tmax.
Pharmacokinetics
- Oral — t½ 43.3 h · F 94% · Vd 88 L
- IV — t½ 43.3 h · F 100% · Vd 88 L
Sources: PMID:1684924, PMID:6784999, PMID:6849499, PMID:10613621, PMID:6790582